title: In silico and in vivo anti-malarial studies of 18β glycyrrhetinic acid from Glycyrrhiza glabra.
abstract: Malaria is one of the most prevailing fatal diseases causing between 1.2 and 2.7 million deaths all over the world each year. Further, development of resistance against the frontline anti-malarial drugs has created an alarming situation, which requires intensive drug discovery to develop new, more effective, affordable and accessible anti-malarial agents possessing novel modes of action. Over the past few years triterpenoids from higher plants have shown a wide range of anti-malarial activities. As a part of our drug discovery program for anti-malarial agents from Indian medicinal plants, roots of Glycyrrhizaglabra were chemically investigated, which resulted in the isolation and characterization of 18β-glycyrrhetinic acid (GA) as a major constituent. The in vitro studies against P. falciparum showed significant (IC50 1.69 µg/ml) anti-malarial potential for GA. Similarly, the molecular docking studies showed adequate docking (LibDock) score of 71.18 for GA and 131.15 for standard anti-malarial drug chloroquine. Further, in silico pharmacokinetic and drug-likeness studies showed that GA possesses drug-like properties. Finally, in vivo evaluation showed a dose dependent anti-malarial activity ranging from 68-100% at doses of 62.5-250 mg/kg on day 8. To the best of our knowledge this is the first ever report on the anti-malarial potential of GA. Further work on optimization of the anti-malarial lead is under progress.
authors.affiliation: Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, Uttar Pradesh, India.
authors.forename: Komal
authors.initials: K
authors.lastname: Kalani
authors.forename: Jyoti
authors.initials: J
authors.lastname: Agarwal
authors.forename: Sarfaraz
authors.initials: S
authors.lastname: Alam
authors.forename: Feroz
authors.initials: F
authors.lastname: Khan
authors.forename: Anirban
authors.initials: A
authors.lastname: Pal
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D001682:Biological Availability; D003198:Computer Simulation; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D006035:Glycyrrhiza / Q000737:chemistry*; D007770:L-Lactate Dehydrogenase / Q000737:chemistry; D016778:Malaria, Falciparum / Q000188:drug therapy; D051379:Mice; D008958:Models, Molecular; D018517:Plant Roots / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology
chemical_list: D000962:Antimalarials; C119129:18alpha-glycyrrhetinic acid; D007770:L-Lactate Dehydrogenase; D006034:Glycyrrhetinic Acid